Shock wave lithotripsy (SWL) is the treatment of choice for renal stone disease and has been a widely accepted and effective treatment. However, as manufacturers seek to deliver new and improved devices, they have generally migrated from units that produce broad focal volumes with moderately-high shock wave amplitudes to tight focal volumes with high shock wave amplitudes. This approach is intended to enhance stone comminution and reduce tissue injury. However, it appears that these manufacturers have discounted the role of cavitation in either stone comminution or tissue injury. Over the past several years, this PPG team has undertaken a broad and comprehensive study of both the physical and the biological mechanisms associated with SWL; this particular project has made considerable progress in examining the role of cavitation and find it to be the dominant mechanism of action. Although we have made much progress, there is still much that is not understood, and this proposal details our continued search to understand the physical mechanisms through which SWL can continue to provide a safe and effective treatment for stone disease. In order for our scientific progress to be optimized, we have concentrated on a general direction meant to transition our discoveries from the laboratory to the manufacturer. Accordingly, in this proposal we seek ways to improve the devices and the approaches to SWL and to disseminate to manufacturers and the general public specific recommendations for such improvements. To this end, our specific aims are summarized as follows: 1) to develop techniques and devices that would provide monitoring feedback on cavitation, blood flow, and stone comminution to clinicians in real-time 2) to use our dual-pulse lithotripter to test our hypothesis that localizing and intensifying the cavitation field will maximize comminution while minimizing tissue injury; 3) to determine whether lithotripter shock waves or the forces produced by cavitation cluster collapse produce the greatest stresses within the stone; 4) to measure the individual effects of the various components of the shock-wave waveform and from this knowledge, design an optimal waveform; and 5) to expand our cavitation model capability by introducing the effect of evaporation within the bubble, and from these studies, obtain estimates of the level of free radical production by SWL.